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Biomedical subjects

R A Andersen

Publications and source records attributed to R A Andersen.

At least 19 recordsLinked to original sources

Head position signals used by parietal neurons to encode locations of visual stimuli.

The mechanism for object location in the environment, and the perception of the external world as stable when eyes, head and body are moved, have long been thought to be centred on the posterior parietal cortex. However, head position signals, and their integration with visual and eye position signals to form a representation of space referenced to the body, have never been examined in any area of the cortex. Here we show that the visual and saccadic activities of parietal neurons are strongly affected by head position. The eye and head position effects are equivalent for individual neurons, indicating that the modulation is a function of gaze direction, regardless of whether the eyes or head are used to direct gaze. These data are consistent with the idea that the posterior parietal cortex contains a distributed representation of space in body-centred coordinates.

Animals

Accumulation of metallothionein and its multiple forms by zinc, cadmium and dexamethasone in human peripheral T and B lymphocytes and monocytes.

Metallothionein (MT) is produced at high rates in isolated monocytes, and T and B lymphocytes during induction in vitro. At optimal concentrations, 125 microM for Zn and 10 microM for Cd and dexamethasone (dex), MT was demonstrated after only 2 h in some cases, and in all cell types substantial levels were measured after 1 day of exposure to all three inductors. With Cd, lower amounts of MT were found, but maximum levels were reached faster than with Zn. The same result was found for dex compared to Zn. Zn and dex in combination showed the same accumulation rate as Zn alone. If the inductors were used in lower concentrations than optimal, reduced accumulation rates occurred, particularly during the first part of the exposure period. No MT was found for concentrations below 5 microM Zn, 1 microM Cd or 0.5 microM dex. The constitutive levels of MT (mean +/- S.E.M.) were 0.11 +/- 0.05, 0.54 +/- 0.3, 0.06 +/- 0.05 and 0.15 +/- 0.08 nmol Cd bound/5 x 10(6) unseparated mononuclear cells (MNC), monocytes, T lymphocytes and B lymphocytes, respectively. Monocytes accumulated 19 times and B lymphocytes 6 times more MT than T lymphocytes after 2 days of exposure to 125 microM Zn. Despite these differences in accumulated amounts of MT, the fold accumulation values were rather similar between the cell types, reflecting corresponding variations in background MT levels. After exposure of unseparated MNC to 125 microM Zn for 2 days, removal of the metal caused constitutive MT levels to be reestablished in 5 days. Five different MT forms, all capable of Cd complexation, were demonstrated in these cells. These forms had kinetically different behaviour during Zn exposure among the cell types, and the response to Cd was different from the Zn response. The results indicate metals to be closely controlled in MNC and emphasize a role for multiple MT forms in the process of regulation.

B-Lymphocytes

Integration of motion and stereopsis in middle temporal cortical area of macaques.

The primate visual system incorporates a highly specialized subsystem for the analysis of motion in the visual field. A key element of this subsystem is the middle temporal (MT) cortical area, which contains a majority of direction-selective neurons. MT neurons are also selective for binocular disparity (depth), which is perplexing given that they are not sensitive to motion through depth. What is the role of disparity in MT? Our data suggest an important link between disparity and transparent motion detection. Motion signals in different directions tend to inhibit each other within a given MT receptive field. This inhibition has an averaging effect which minimizes MT responses to random motion signals created by light intensity changes and other non-motion stimuli (motion noise). But, in the absence of disparity cues, inhibition may also occur between surfaces moving in different directions through the same part of the visual field (transparent motion), thus impairing the detection of either surface. Here we show that inhibition in MT occurs mainly between motion signals with similar disparities. Transparent surface movements at different depths are thus represented independently in MT (that is, without inhibiting each other) whereas spurious motion signals from a given surface tend to cancel out. To our knowledge, these results provide the first evidence for a functional integration of motion and disparity in MT.

Animals

Cladistic analyses of combined traditional and molecular data sets reveal an algal lineage.

The chromophyte algae are a large and biologically diverse assemblage of brown seaweeds, diatoms, and other golden algae classified in 13 taxonomic classes. One subgroup (diatoms, pedinellids, pelagophytes, silicoflagellates, and certain enigmatic genera) is characterized by a highly reduced flagellar apparatus. The flagellar apparatus lacks microtubular and fibrous roots, and the flagellum basal body is attached directly to the nucleus. We hypothesize that the flagellar reduction is the result of a single evolutionary series of events. Cladistic analysis of ultrastructural and biochemical data reveals a monophyletic group that unites all taxa with a reduced flagellar apparatus, supporting our hypothesis. Phylogenetic analyses of 18S rRNA gene sequence data provide strong resolution within most of the major groups of chromophytes but only weakly resolve relationships among those groups. Some of the molecularly based most parsimonious trees, however, also unite the taxa with a reduced flagellar apparatus, although the diatoms are not included in this lineage. This grouping is further supported by a posteriori character weighting of the molecular data, suggesting that flagellar reduction occurred at least twice in parallel evolutionary series of events. To further test our hypothesis of a single evolutionary reduction in the flagellar apparatus, we combine the two data sets and subject the hybrid data matrix to parsimony analysis. The resulting trees unite the diatoms with the other reduced flagellar apparatus algae in a monophyletic group. This result supports our hypothesis of a single evolutionary reduction and indicates the existence of a previously unrecognized lineage of algae characterized by a highly reduced flagellar apparatus. Further, this study suggests that the traditional classification of the diatoms with the chrysophytes and xanthophytes in the division (= phylum) Chrysophyta, as presented in most textbooks, is unsatisfactory and that a significantly different classification should be employed.

Base Sequence

V1 responses to transparent and nontransparent motions.

It is well known that a stimulus composed of two independent sets of random dots moving in opposite directions produces a percept of two overlapping transparent surfaces moving across each other, while a counterphase grating composed of two identical sine wave gratings drifting in opposite directions does not. We recorded from the directionally selective V1 cells of behaving macaque monkeys using these two types of stimuli in order to investigate the physiological basis of transparent motion perception. Previous single-unit recording experiments from our laboratory indicated that many V1 cells respond well to transparent random dot patterns, while MT cells' responses to the same patterns are strongly suppressed in comparison with their preferred direction responses. This observation alone would seem to suggest that V1 activity could better explain transparent motion perception than MT activity. However, one could argue to the contrary based on the psychophysical observation that there is a motion threshold elevation under the transparency condition. We decided to determine the correlation between V1 activity and the transparent motion perception directly by recording from V1 cells using both transparent random dot patterns and nontransparent counterphase gratings. It is found that V1 cells on the average could not reliably tell the two types of patterns apart. Our results further the idea that additional processing beyond V1 is involved in transparent motion analysis.

Animals

Recovering three-dimensional structure from motion with surface reconstruction.

This paper addresses the computational role that the construction of a complete surface representation may play in the recovery of 3-D structure from motion. We first discuss the need to integrate surface reconstruction with the structure-from-motion process, both on computational and perceptual grounds. We then present a model that combines a feature-based structure-from-motion algorithm with a smooth surface interpolation mechanism. This model allows multiple surfaces to be represented in a given viewing direction, incorporates constraints on surface structure from object boundaries, and segregates image features onto multiple surfaces on the basis of their 2-D image motion. We present the results of computer simulations that relate the qualitative behavior of this model to psychophysical observations. In a companion paper, we discuss further perceptual observations regarding the possible role of surface reconstruction in the human recovery of 3-D structure from motion.

Algorithms

Structure-from-motion: perceptual evidence for surface interpolation.

Dynamic random-dot displays representing a rotating cylinder were used to investigate surface interpolation in the perception of structure-from-motion (SFM) in humans. Surface interpolation refers to a process in which a complete surface in depth is reconstructed from the object depth values extracted at the stimulus features. Surface interpolation will assign depth values even in parts of the object that contain no features. Such a "fill-in" process should make the detection of featureless stimulus areas ("holes") difficult. Indeed, we demonstrate that such holes in our rotating cylinder can be as wide as one-quarter of the stimulus before subjects can reliably detect their presence. Subjects were presented with a variation on the rotating cylinder in which all dots were oscillating either in synchrony or asynchronously. Subjects perceive a rigidly rotating cylinder even when such a percept is not in agreement with the physical stimulus. To reconcile this discrepancy between actual and perceived stimulus we propose that individual points contribute to a surface based object representation and that in this process the visual system looses access to the identity of the individual features that make up the surface. Finally we are able to explain a variety of previously documented perceptual peculiarities in the perception of structure-from-motion by arguing that the perceptual interpretation of the object's boundaries influences the surface interpolation process. These findings offer strong perceptual evidence for a process of surface interpolation and are also physiologically plausible given results from recordings in awake behaving monkey cortical areas V1 and MT. The companion paper demonstrates how such a surface interpolation process can be incorporated into a structure-from-motion algorithm and how object boundaries can influence the perception of structure-from-motion as has been demonstrated before and in this paper.

Depth Perception

Cytotoxicity and accumulation of Hg, Ag, Cd, Cu, Pb and Zn in human peripheral T and B lymphocytes and monocytes in vitro.

1. The cytotoxic effects of various heavy metals were assayed by trypan blue exclusion in vitro in human peripheral immune cells separated to high purity. T and B lymphocytes and monocytes were equally sensitive to metals. The individual metals could be ranked in the following decreasing order of cytotoxic potency, Hg approximately Ag > Cd approximately Cu > Pb approximately Zn, based on exposure time and concentration needed to give a particular percentage of dead cells. 2. The cytotoxic effects became irreversible after about 13 hr of metal exposure. 3. Examination by scanning electron microscopy showed that the heavy metals caused serious destruction of the cell membranes. 4. Solubility and uptake of metals into the cells were studied and discussed in relation to the cytotoxic effects. It was concluded that metal binding to cell surfaces or precipitate formation could inhibit ordinary uptake, thereby affecting cytotoxicity. For Pb in monocytes this appeared to lead to uptake of non-toxic complexes, probably by phagocytosis.

Adult

Transparent motion perception as detection of unbalanced motion signals. I. Psychophysics.

Our visual system can solve the difficult problem of representing multiple motions in the same part of the visual space, the motion transparency problem. We investigated the conditions under which transparent motion perception occurs through psychophysical observations, using a series of visual displays composed of two simple patterns moving in opposite directions. We found that whenever a display has finely balanced opposing motion signals in all local regions, it is perceptually nontransparent. The displays that appeared transparent always contain locally unbalanced motion signals, with some local regions having net motion signals in one direction and some other regions in the opposite direction. These interdigitating net motion signals in both directions appear to be integrated separately to form two overlapping transparent surfaces. Displays that were spatially balanced could be made perceptually transparent if the two components moving in opposite directions were at different stereo depth planes or had different spatial frequency contents. Our results can be explained by proposing a disparity- and spatial frequency-specific suppression stage in the motion pathway, at which motion signals of different directions, but of the same disparity and spatial frequency contents, locally inhibit each other. Such a mechanism would suppress noise input to the motion system, which generally activates several direction channels simultaneously, and would still not eliminate activity evoked by transparent surfaces that are at different depths or have different textures.

Cues

Transparent motion perception as detection of unbalanced motion signals. II. Physiology.

We investigated how the primate visual system solves the difficult problem of representing multiple motion vectors in the same part of the visual space--the problem of motion transparency. In the preceding companion article we reported that displays with locally well-balanced motion signals in opposite directions are perceptually nontransparent (i.e., one does not see two coherent moving surfaces) and that transparent displays always contain locally unbalanced motion signals. This is exemplified by our paired and unpaired dot patterns. Although both types of stimuli contain two sets of dots moving in opposite directions, the former is locally well balanced and appears like flicker while the latter gives a perception of two transparent surfaces. In this article we report our physiological recordings from areas V1 and MT of behaving monkeys, comparing single-cell responses to the paired and the unpaired dot patterns. Although a small proportion of directionally selective V1 cells responded differently to the two types of patterns, the average V1 responses could not reliably distinguish between the paired and the unpaired stimuli. A large fraction of MT cells, on the other hand, responded significantly better to the unpaired dot patterns than to the paired ones. Furthermore, the average response of all MT cells to the unpaired dot patterns was significantly higher than that to the paired dot patterns. These results demonstrate a neural correlate of the perceptual transparency at the level of MT. On the other hand, V1 cells do not generally discriminate between the transparent and nontransparent stimuli, indicating that V1 activity is not well correlated with the perception of motion transparency. Our results are consistent with a two-stage model for motion processing: the first stage measures local motion and the second stage introduces suppression if different directions of motion are present at a local region of the visual field. The first stage is located primarily in V1 and the second stage primarily in MT. Finally, we found a strong and negative correlation between the degree of the opponent-direction suppression of MT cells and their responses to flicker noise stimuli. This result suggests that one of the fundamental roles of the opponent-direction suppression in MT is noise reduction.

Animals

Transparent motion perception as detection of unbalanced motion signals. III. Modeling.

In the preceding two companion articles we studied the conditions under which transparent motion perception occurs through psychophysical experiments, and investigated the underlining neural mechanisms through physiological recordings. The main finding of our perceptual experiments was that whenever a display has finely balanced motion signals in all local areas, it is perceptually nontransparent, and that transparent displays always contain motion signals in different directions that are either spatially unbalanced, or unbalanced in their disparity or spatial frequency contents. In the physiological experiments, we found two stages in the processing of transparent stimuli. The first stage is located primarily in area V1. At this stage motion measurements are made and V1 cells respond well to both the balanced, nontransparent stimuli and the unbalanced, perceptually transparent stimuli. The second stage is located primarily in area MT. MT cells show strong suppression between opposite directions of motion. The suppression for the unbalanced, transparent stimuli is significantly less than that for the balanced, nontransparent stimuli. Therefore, the activity in the second, MT stage correlates better with the perception of motion transparency than the first, V1 stage, which does not distinguish reliably between transparent and nontransparent motion. The above experiments suggest a two-stage model of motion perception with a motion measurement stage in V1 and an opponent-direction suppression stage in area MT. In this article we explicitly test this model through analysis and computer simulations, and compare the response of the model to the perceptual and physiological results using the same balanced and unbalanced stimuli we used in the experiments. In the first stage of the computational model, motion energies in different spatial frequency and disparity ranges are extracted from each local region. Similar to V1, this stage does not distinguish between the balanced and unbalanced stimuli. In the subsequent stage motion energies of opposite directions but with same spatial frequency and disparity contents suppress each other using subtractive or divisive inhibition. This stage responds significantly better to the transparent stimuli than to the nontransparent ones, in agreement with MT activity.

Animals

The response of neurons in areas V1 and MT of the alert rhesus monkey to moving random dot patterns.

We studied the response of single units to moving random dot patterns in areas V1 and MT of the alert macaque monkey. Most cells could be driven by such patterns; however, many cells in V1 did not give a consistent response but fired at a particular point during stimulus presentation. Thus different dot patterns can produce a markedly different response at any particular time, though the time averaged response is similar. A comparison of the directionality of cells in both V1 and MT using random dot patterns shows the cells of MT to be far more directional. In addition our estimates of the percentage of directional cells in both areas are consistent with previous reports using other stimuli. However, we failed to find a bimodality of directionality in V1 which has been reported in some other studies. The variance associated with response was determined for individual cells. In both areas the variance was found to be approximately equal to the mean response, indicating little difference between extrastriate and striate cortex. These estimates are in broad agreement (though the variance appears a little lower) with those of V1 cells of the anesthetized cat. The response of MT cells was simulated on a computer from the estimates derived from the single unit recordings. While the direction tuning of MT cells is quite wide (mean half-width at half-height approximately 50 degrees) it is shown that the cells can reliably discriminate much smaller changes in direction, and the performance of the cells with the smallest discriminanda were comparable to thresholds measured with human subjects using the same stimuli (approximately 1.1 degrees). Minimum discriminanda for individual cells occurred not at the preferred direction, that is, the peak of their tuning curves, but rather on the steep flanks of their tuning curves. This result suggests that the cells which may mediate the discrimination of motion direction may not be the cells most sensitive to that direction.

Animals

Evidence for the lateral intraparietal area as the parietal eye field.

It has long been appreciated that the posterior parietal cortex plays a role in the processing of saccadic eye movements. Only recently has it been discovered that a small cortical area, the lateral intraparietal area, within this much larger area appears to be specialized for saccadic eye movements. Unlike other cortical areas in the posterior parietal cortex, the lateral intraparietal area has strong anatomical connections to other saccade centers, and its cells have saccade-related responses that begin before the saccades. The lateral intraparietal area appears to be neither a strictly visual nor strictly motor structure; rather it performs visuomotor integration functions including determining the spatial location of saccade targets and forming plans to make eye movements.

Animals

A more biologically plausible learning rule for neural networks.

Many recent studies have used artificial neural network algorithms to model how the brain might process information. However, back-propagation learning, the method that is generally used to train these networks, is distinctly "unbiological." We describe here a more biologically plausible learning rule, using reinforcement learning, which we have applied to the problem of how area 7a in the posterior parietal cortex of monkeys might represent visual space in head-centered coordinates. The network behaves similarly to networks trained by using back-propagation and to neurons recorded in area 7a. These results show that a neural network does not require back propagation to acquire biologically interesting properties.

Animals

Sensorimotor transformation during eye movements to remembered visual targets.

For eye movements made to visual targets, the brain must transform the retinotopic coordinate frame of the visual system to that of the oculomotor plant. Ideally, responses should exactly match target demands. However, during eye movements to remembered targets, responses are spatially distorted. The transformation does not retain accurate retinotopic registration, having both constant and variable components of error. Generally, the constant pattern of distortion appears as a hypermetria for upward saccades and a hypometria for downward movements. Most of the error accumulates during the first 800 msec of memory-contingent delay. The results are interpreted with respect to theories of how spatial information may be coded and transformed.

Animals

Human perception of structure from motion.

Novel dynamic random-do displays representing a rotating cylinder or a noise-field were used to investigate the perception of structure from motion (SFM) in humans. The finite lifetimes of the points allowed the study of spatiotemporal characteristics with smoothly moving stimuli. In one set of experiments subjects had to detect the change from the unstructured motion to the appearance of the cylinder in a reaction time task. In another set of experiments subjects had to distinguish these two stimuli in a two-alternative forced-choice task. The two major findings were: (1) a relatively constant point lifetime threshold (50-85 msec) for perceiving structure from motion. This threshold is similar to the threshold for estimating velocity and suggests that velocity measurements are used to process SFM; (2) long reaction times for detecting structure (approximately 1 sec). The build-up of performance with time and with increasing numbers of points reflects a process of temporal and spatial integration. We propose that this integration is achieved through the generation of a surface representation of the object. Information from single features on the object appears to be used to interpolate a surface between these local measurements allowing the system to improve perception over extended periods of time even though each feature is present only briefly. Selective masking of the stimulus produced characteristic impairments which suggest that both velocity measurements and surface interpolation are global processes.

Form Perception

Effect of the metal in the reaction between metallothionein and antimetallothionein antibody.

1. An antimetallothionein antibody, raised against Cd-carrying metallothionein, was applied in Western blotting of metallothionein. 2. Treatment of the electroblotted nitrocellulose sheets with metals belonging to the periodic system transition groups Ib and IIb, or with Pb, Ni or Cr, considerably enhanced binding of anti-metallothionein. A similar effect was found when the electroblotted sheets were treated with the strong alkylator N-ethylmaleimide. 3. It seems that the binding of metal to metallothionein modifies the configuration of the antibody binding sites by the formation of metal thiolate complexes. 4. Metal treatment of the nitrocellulose sheets after electroblotting, but before application of the primary antibody, offers a convenient method for use in Western blotting to significantly potentiate the reaction between metallothionein and the antimetallothionein antibody.

Alkylation

Reductive metabolism and protein binding of chromium(VI) by P450 protein enzymes.

The cytochrome P450-dependent reduction of Cr(VI) using reconstituted phospholipid vesicles containing purified preparation of various forms of rabbit and rat liver microsomal cytochrome P450 has been investigated. The alcohol-induced form of the rat, P450IIE1, was the most efficient enzyme, 7.2 +/- 0.40 nmol Cr/nmol P450/min, whereas the corresponding rates for rat P450IA1, rat IIB1, rabbit IIB4, rabbit IA2 and rabbit IIE1 were 1.7 +/- 0.09, 2.5 +/- 0.08, 1.6 +/- 0.08, 2.5 +/- 0.15 and 1.6 +/- 0.08 nmol Cr/nmol P450/min respectively. NADPH-cytochrome P450 reductase had Cr(VI) reductase activity which was dependent on enzyme concentration. Below 0.15 nmol P450 reductase/ml the sp. act. was low and constant, while at a higher concentration the activity was markedly dependent upon the amount of enzyme present. In a quantitative binding assay it was shown that binding of [51Cr]Cr(VI) to the catalytic enzymes was proportional to the enzyme concentration up to 0.8 nmol P450/ml, which caused binding of 70% of the total radioactivity. Analysis by SDS-PAGE and autoradiography exhibited binding to the individual catalytic proteins of [51Cr]Cr. EDTA treatment removed the radioactivity from the bands matching P450 and P450 reductase, indicating that Cr(III) is bound to the proteins. The reducing activity of both P450 and P450 reductase was potently inhibited by oxygen. The inhibitory effect of oxygen is not due to reoxidation of the reduced Cr and redox cycling. Rat P450IA1 ethoxycoumarin O deethylase activity was inhibited after preincubation with chromate (CrO4(2-). The P450 reductase inhibitor 2'-AMP stimulated the anaerobic P450 reductase dependent Cr(VI) reductase rate approximately 2-fold. Both CO and CCl4 inhibited the different P450 enzymes to various extents. With rabbit P450IIE1 CCl4 stimulated the Cr(VI) reduction approximately 4-fold, whereas the activity of the other enzymes was inhibited when the reconstituted system was incubated with CrO4(2-) and CCl4 prior to NADPH addition. Neither CO nor CCl4 affected the Cr(VI) reducing activity of the P450 reductase. The difference in CrO4(2-) reducing activity of the P450 enzymes and binding to the enzymes may be important for in vivo endoplasmic catalytic metabolism of CrO4(2-).

7-Alkoxycoumarin O-Dealkylase